{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:08:37Z","timestamp":1789060117858,"version":"build-2803163510"},"reference-count":67,"publisher":"Institution of Engineering and Technology (IET)","issue":"1","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":270,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003213","name":"Beijing Municipal Education Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003213","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ietresearch.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IET Systems Biology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pancreatic adenocarcinoma (PAAD) remains highly lethal because of chemotherapy resistance and immunosuppressive microenvironments. Tertiary lymphoid structures (TLSs) were analysed in PAAD to develop personalised therapeutic strategies. Nine TLS\u2010related genes (\n                    <jats:italic>CCR6<\/jats:italic>\n                    ,\n                    <jats:italic>CD1d<\/jats:italic>\n                    ,\n                    <jats:italic>CD79B<\/jats:italic>\n                    ,\n                    <jats:italic>CETP<\/jats:italic>\n                    ,\n                    <jats:italic>EIF1AY<\/jats:italic>\n                    ,\n                    <jats:italic>LAT<\/jats:italic>\n                    ,\n                    <jats:italic>PTGDS<\/jats:italic>\n                    ,\n                    <jats:italic>RBP5<\/jats:italic>\n                    and\n                    <jats:italic>SKAP1<\/jats:italic>\n                    ) were selected for integrative analysis of TLS status in relation to clinical outcomes, immune cell infiltration, tumour mutational burden (TMB) and drug resistance. High TLS scores (TLS_H) were associated with improved overall survival (OS) and progression\u2010free survival (PFS), independent of age or tumour grade. Twelve immune cell types differed across TLSs. Single\u2010cell RNA\u2010seq analysis revealed that the 9 TLS\u2010related genes were enriched in distinct immune cell populations. Combining TLS and TMB improved survival prediction. Notably, the TLS_H group demonstrated enhanced sensitivity to chemotherapeutics including AZD8055, axitinib, vorinostat, nilotinib, camptothecin and paclitaxel. Real\u2010time fluorescent quantitative PCR (RT\u2010qPCR) validation in Mia PaCa2 and Jurkat cells indicated that\n                    <jats:italic>LAT<\/jats:italic>\n                    ,\n                    <jats:italic>RBP5<\/jats:italic>\n                    and\n                    <jats:italic>SKAP1<\/jats:italic>\n                    may play important roles in modulating sensitivity to these chemotherapeutics. These findings establish TLS as a potential biomarker for PAAD, enabling personalised chemotherapy selection by integrating immune contexture and genomic drivers to improve clinical outcomes.\n                  <\/jats:p>","DOI":"10.1049\/syb2.70038","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T01:40:25Z","timestamp":1759110025000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Integrative Analysis of TLS\u2010Associated Gene Signatures, Immune Infiltration and Drug Sensitivity in Pancreatic Cancer"],"prefix":"10.1049","volume":"19","author":[{"given":"Mengzhou","family":"Gao","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of Enze Biomass Fine Chemicals College of New Materials and Chemical Engineering Beijing Institute of Petrochemical Technology  Beijing 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